Muscular dystrophy refers to a group of more than 30 hereditary muscle diseases characterized by progressive skeletal muscle weakness, degeneration of skeletal muscle fibers, defects in certain muscle proteins, and death of muscle cells and tissue. As muscular dystrophy progresses and muscles weaken, fixations (contractures) can develop in joints, in which muscles and tendons shorten, restricting the flexibility and mobility of joints and muscles. Muscular dystrophies are multi-system disorders with manifestations in numerous body systems including the heart, gastrointestinal and nervous systems, endocrine glands, skin, eyes, and other organs.
Duchenne muscular dystrophy is the most common childhood form of muscular dystrophy, affecting about 1 out of every 3500 males. Duchenne muscular dystrophy is characterized by a near complete lack of dystrophin protein production, which most often is caused by mutations in the gene coding for dystrophin. Signs and symptoms of Duchenne muscular dystrophy usually appear between the ages of 2 and 6, first affecting the muscles of the pelvis, upper arms, and upper legs. By late childhood, most children with Duchenne muscular dystrophy are unable to walk and most die in their late teens or early 20s, often from respiratory muscle weakness or cardiac complications. Other forms of muscular dystrophy include Becker's muscular dystrophy, a less severe form of Duchenne muscular dystrophy in which a partially functional (i.e., truncated) form of dystrophin is produced, congenital muscular dystrophy, distal muscular dystrophy, Emery-Dreifuss muscular dystrophy, facioscapulohumeral muscular dystrophy, limb-girdle muscular dystrophy, myotonic muscular dystrophy, and oculopharyngeal muscular dystrophy.
There is currently no cure for any form of muscular dystrophy. Respiratory therapy, physical therapy to prevent contractures and maintain muscle tone, use of orthopedic appliances for support, and corrective orthopedic surgery are often used to improve quality of life. Current therapeutic approaches to muscular dystrophies involve administration of steroids (e.g., glucocorticoids, corticosteroiods), such as, for example, prednisone or deflazacort. These treatments result in modest benefits and are often accompanied by undesirable side effects, including, for example, osteoporosis, hypertension, and weight gain. Thus, there is a need in the art for methods and agents useful for effectively treating muscular dystrophy, for reducing the progression and severity of muscular dystrophy, and for preventing or treating one or more symptoms of muscular dystrophy.
The present invention meets this need by providing novel methods and agents for use in treating muscular dystrophy. In particular, the present invention provides methods and agents for the treatment of muscular dystrophy by inhibiting connective tissue growth factor (CTGF) activity or expression.